3.1 Protection of Human Subjects

Instructions:

  1. Risks to Human Subjects
  2. Human Subjects Involvement, Characteristics, and Design

Briefly describe the overall study design.

Describe the subject population(s) to be included in the study; the procedures for assignment to a study group, if relevant; and the anticipated numbers of subjects for each study group.

List any collaborating sites where human subjects research will be performed, and describe the role of those sites and collaborating investigators in performing the proposed research.

Note on Forms E Updates for This Section: Items Removed: Justification for proposed use of human subjects, description of age range and health status of subject population; sample plan, and rationale for involvement of vulnerable populations (see new Section 2. Adequacy of Protection Against Risks, Section c. Vulnerable Populations). Items Added: Study design.

  1. Study Procedures, Materials, and Potential Risks

Describe all planned research procedures (interventions and interactions) involving study subjects; how research material, including biospecimens, data, and/or records, will be obtained; and whether any private identifiable information will be collected in the proposed research project.

For studies that will include the use of previously collected biospecimens, data or records, describe the source of these materials, whether these can be linked with living individuals, and who will be able to link the materials.

Describe all the potential risks to subjects associated with each study intervention, procedure or interaction, including physical, psychological, social, cultural, financial, and legal risks; risks to privacy and/or confidentiality; or other risks. Discuss the risk level and the likely impact to subjects.

Where appropriate, describe alternative treatments and procedures, including their risks and potential benefits. When alternative treatments or procedures are possible, make the rationale for the proposed approach clear.

Note on Forms E Updates for This Section: Items Removed:“Sources of Material” changed to “Study Procedures, Materials, and Potential Risks” (Separate Sources and Risks removed); Items Added: details on previously collected biospecimen considerations; considerations for specifying potential risks for each intervention separately.

  1. Adequacy of Protection Against Risks
  2. Informed Consent and Assent

Describe the process for obtaining informed consent. Include a description of the circumstances under which consent will be sought and obtained, who will seek it, the nature of the information to be provided to prospective subjects, and the method of documenting consent. When appropriate, describe how potential adult subjects’ capacity to consent will be determined and the plans for obtaining consent from a legally authorized representative for adult subjects not able to consent.

For research involving children: If the proposed studies will include children, describe the process for meeting HHS regulatory requirements for parental permission and child assent (45 CFR 46.408). See the HHS page on Research with Children FAQs and the NIH page on Requirements for Child Assent and Parent/Guardian Permission.

If a waiver of some or all of the elements of informed consent will be sought, provide justification for the waiver. Do not submit informed consent document(s) with your application unless you are requested to do so.

Note on Forms E Updates for This Section: Items Removed: Recruitment has been removed from this section. See Separate Upload, 2.5 Recruitment and Retention Plan. Items Added:Emphasis on caveats for adults unable to consent.

  1. Protections Against Risk

Describe planned strategies for protecting against or minimizing all potential risks identified, including strategies to manage and protect the privacy of participants and confidentiality of research data.

Where appropriate, discuss plans for ensuring necessary medical or professional intervention in the event of adverse effects on participants.

Describe plans for handling incidental findings, such as those from research imaging, screening tests, or paternity tests.

Note on Forms E Updates for This Section: Items Added:Incidental findings.

  1. Vulnerable Subjects, if relevant to your study

Explain the rationale for the involvement of special vulnerable populations, such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations. 'Prisoners' includes all subjects involuntarily incarcerated (for example, in detention centers).

Pregnant Women, Fetuses, and Neonates or Children

If the study involves vulnerable subjects subject to additional protections under Subparts B and D (pregnant women, fetuses, and neonates or children), provide a clear description of the risk level and additional protections necessary to meet the HHS regulatory requirements.

Prisoners

If the study involves vulnerable subjects subject to additional protections under Subpart C (prisoners), describe how proposed research meets the additional regulatory requirements, protections, and plans to obtain OHRP certification for the involvement of prisoners in research.

Note on Forms E Updates for This Section: Items Added:This is an entirely new section replacing separate components into a single consolidated Vulnerable Populations category.

  1. Potential Benefits of the Proposed Research to Research Participants and Others

Discuss the potential benefits of the research to research participants and others.

Discuss why the risks to subjects are reasonable in relation to the anticipated benefits to research participants and others.

Note: Financial compensation of subjects should not be presented as a benefit of participation in research.

Note on Forms E Updates for This Section: Items Added:Clarification that compensation is not a benefit.

  1. Importance of the Knowledge to be Gained

Discuss the importance of the knowledge to be gained as a result of the proposed research.

Discuss why the risks to subjects are reasonable in relation to the importance of the knowledge that reasonably may be expected to result.

Note on Forms E Updates for This Section: Items Removed:FDA IND/IDE test articles has been removed from this section. See Separate Upload, 4.6 FDA Investigational Product, investigational New Drug (IND), and Investigational Device Exemption (IDE) Status.